1. Introduction
The following description includes information that may be useful in understanding the present invention. It is not an admission that any of the information provided herein, or any publication specifically or implicitly referenced herein, is prior art, or even particularly relevant, to the presently claimed invention.
2. Background
The multiplicity and diversity of roles for mineral elements ensures that essential metabolic reactions are maintained for an organism's life cycle. The importance of calcium, for example, is exemplified by its essentiality not only to the development and maintenance of the skeleton, but also by its role in specific enzyme activation and other biochemical and physiological parameters.
Deposition of mineral salts (e.g., calcium salts) can be triggered by tissue trauma or other signals such as abnormal fluctuations in intracellular calcium ion concentrations. Accordingly, detection and analysis of calcium crystal species, as well as other crystal species, could be important in diagnosing and managing various diseases.
3. Definitions
Before describing the instant invention in detail, several terms used in the context of the present invention will be defined. In addition to these terms, others are defined elsewhere in the specification, as necessary. Unless otherwise expressly defined herein, terms of art used in this specification will have their art-recognized meanings.
The term “antibody” herein is used in the broadest sense and specifically covers monoclonal antibodies (including full length monoclonal antibodies), polyclonal antibodies, multispecific antibodies (e.g., bispecific antibodies), antibody fragments, chimeric antibodies, and binding agents that employ the CDRs (or variant thereof that retain antigen binding activity) of the parent antibody. Antibodies retain at least one desired activity of the parent antibody. Desired activities can include the ability to bind the antigen, or epitope-containing peptide, specifically. “Antibody fragments” comprise a portion of a full-length antibody, generally the antigen binding or variable domain thereof. Examples of antibody fragments include Fab, Fab′, F(ab′)2, and Fv fragments; diabodies; linear antibodies; single-chain antibody molecules; and multispecific antibodies formed from antibody fragments.
“Basic calcium phosphate” or “BCP” refers to carbonate-substitute apatite, octacalcium phosphate, and tricalcium phosphate.
A “biological sample” refers to a sample taken from a patient or subject. Such samples include tissue samples and fluid samples. A “fluid sample” includes a sample of a patient's blood, plasma, serum, urine, cerebrospinal fluid, lymph, synovial fluid, bile, semen, saliva, tears, and aqueous or vitreous humor.
A “label” refers to a detectable compound or composition that is conjugated directly or indirectly to another molecule to allow detection. The label may itself be detectable (e.g., radioisotope labels or fluorescent labels) or, in the case of an enzymatic label, may catalyze chemical alteration of a substrate compound or composition that is detectable. A label may also be a ligand for another molecule, such as one member of a high affinity binding pair (e.g., a ligand and its receptor, an antigen (or antigenic peptide) and an antibody specifically reactive against the antigen, biotin and avidin, etc.).
“Mammal” for purposes of treatment refers to any animal classified as a mammal, including humans, domestic and farm animals, and zoo, sports, or pet animals, such as dogs, horses, cats, cows, etc.
A “patentable” composition, process, machine, or article of manufacture means that the subject matter satisfies all statutory requirements for patentability at the time the analysis is performed. For example, with regard to novelty, non-obviousness, or the like, if later investigation reveals that one or more claims encompass one or more embodiments that would negate novelty, non-obviousness, etc., the claim(s), being limited by definition to “patentable” embodiments, specifically exclude the unpatentable embodiment(s). Also, the claims appended hereto are to be interpreted both to provide the broadest reasonable scope, as well as to preserve their validity. Furthermore, the claims are to be interpreted in a way that (1) preserves their validity and (2) provides the broadest reasonable interpretation under the circumstances, if one or more of the statutory requirements for patentability are amended or if the standards change for assessing whether a particular statutory requirement for patentability is satisfied from the time this application is filed or issues as a patent to a time the validity of one or more of the appended claims is questioned.
A “plurality” means more than one.
The terms “separated”, “purified”, “isolated”, and the like mean that one or more components of a sample are or have been physically removed from, or diluted in the presence of, one or more other sample components. Sample components that may be removed or diluted during a separating or purifying step include, chemical reaction products, unreacted chemicals, proteins, carbohydrates, lipids, and unbound molecules.
By “solid phase” is meant a non-aqueous matrix to which a binding reagent can adhere. Examples of solid phases include those formed partially or entirely of glass (e.g. controlled pore glass), polysaccharides (e.g., agarose), polyacrylamides, polystyrene, polyvinyl alcohol, and silicones. In certain embodiments, depending on the context, the solid phase can comprise the well of an assay plate, a portion of a diagnostic device, etc.
The term “species” refers to a population of chemically indistinct molecules.
“Specifically associate” and “specific association” and the like refer to a specific, non-random interaction between two molecules, which interaction depends on the presence of structural, hydrophobic/hydrophilic, and/or electrostatic features that allow appropriate chemical or molecular interactions between the molecules.
A “subject” or “patient” refers to an animal known to have or suspected of having a disease, disorder, or injury in need of diagnosis and/or treatment. Animals include vertebrates, with mammals such as bovine, canine, equine, feline, ovine, porcine, and primate (including humans and non-humans primates) animals being particularly preferred examples.
The methods and kits of the invention are useful in diagnosis and treatment. “Therapy” refers to the prevention and/or treatment of diseases, disorders, or physical trauma. The term “therapeutic” encompasses the full spectrum of treatments for a disease, disorder, or injury. A “therapeutic” agent may act in a manner that is prophylactic or preventive, including those that incorporate procedures designed to target individuals that can be identified as being at risk (pharmacogenetics); or in a manner that is ameliorative or curative in nature; or may act to slow the rate or extent of the progression of at least one symptom of a disease or disorder being treated; or may act to minimize the time required, the occurrence or extent of any discomfort or pain, or physical limitations associated with recuperation from a disease, disorder or physical trauma; or may be used as an adjuvant to other therapies and treatments.
“Treatment” refers to both therapeutic treatment and prophylactic or preventative measures. Those in need of treatment include those already with the disorder as well as those in which the disorder is to be prevented.